Allon Therapeutics, Inc. Shows Statistically Significant Improvement in Schizophrenia Imaging Study
Allon said statistically significant (p=0.0170) increased levels of N-acetyl aspartate (NAA) were measured in the brains of the schizophrenia patients treated with davunetide using magnetic resonance spectroscopy (MRS). The scientific literature shows that NAA is an informative biomarker because decreased levels of NAA occur in schizophrenia, and in numerous other neurodegenerative conditions such as brain injury, stroke, and Alzheimer's disease.
The study specifically measured NAA from the dorsolateral prefrontal cortex, an area of the brain known to be affected in schizophrenia patients generally and associated with cognitive impairment particularly. These results were obtained with davunetide doses already known to be active in human clinical trials. Interestingly, these results appear to correlate with the davunetide-dependent behavioural outcomes in these same patients.
These data were collected as part of a larger Phase 2a trial for which the clinical data released in 2009 showed that davunetide treatment did not show an advantage compared to placebo on the primary measure, the composite score on the MATRICS Consensus Cognitive Battery. However, it achieved statistically significant efficacy (p=0.015) on the UCSD (University of California at San Diego) Performance-based Skills Assessment (UPSA). The UPSA scale assesses the functional capacity of skills for daily living and has been recognized by drug regulators as an appropriate co-primary endpoint in patients suffering from cognitive impairment associated with schizophrenia (CIAS).
The imaging study was led by researchers at Columbia University in New York City and the New York State Psychiatric Institute (NYSPI), with funding from the National Alliance for Research on Schizophrenia and Depression (NARSAD) and Allon. The Phase 2a trial was managed by TURNS (Treatment Units for Research on Neurocognition and Schizophrenia), a clinical trial network consisting of eight academic medical institutions led by the University of California at Los Angeles, with substantial financial support from the National Institute of Mental Health (NIMH), part of the U.S. National Institutes of Health.
Gordon McCauley, Allon's President and CEO, said these imaging results add clear biomarker validation to the Phase 2a clinical trial results demonstrating the potential of davunetide to be developed and approved as the first drug to treat CIAS.
"Cognitive impairment in schizophrenia is debilitating for millions of patients and their families," McCauley said. "The data continue to accumulate suggesting that davunetide could be the first therapy approved to treat the cognitive impairment that is the real impediment to schizophrenia patients returning to active participation in society."
McCauley also said the imaging data reconfirm the potential of davunetide to treat cognitive impairment and dementia, including Alzheimer's disease.
-- In 2008, Allon reported Phase 2a results showing that davunetide had a statistically significant positive impact on memory function in patients with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer's disease (AD). -- On January 26, 2010, Allon announced the commencement of a clinical trial program evaluating davunetide as a treatment for progressive supranuclear palsy (PSP), one of a group of progressive disorders called frontotemporal dementia (FTD). PSP affects the frontal and temporal lobes of the brain and there are no approved treatments.
Dr. Jeffrey Lieberman, Chairman of the Department of Psychiatry at Columbia University School of Physicians and Surgeons and Director of the New York Psychiatric Institute said the imaging results are consistent with the hypothesis that davunetide can improve brain cell function by repairing and stabilizing microtubules. Microtubules are protein structures important in brain cell shape and function.
"The increase in NAA from our imaging data, the positive outcomes in the Phase 2a trial, plus positive cognitive data from previous animal studies, make a compelling clinical and scientific case for the potential of this compound," said Lieberman.
"An approved treatment for CIAS is urgently needed. We know that it is CIAS - more than psychosis - that has the biggest impact on the ability of schizophrenia patients to manage their lives and to make productive contributions to society," said Lieberman.
The MRS study was a substudy of the Phase 2a clinical trial. In this study, NAA levels before and after 12 weeks of treatment with davunetide were evaluated in 18 chronic schizophrenia patients among the 54 who completed the Phase 2a trial. Of the 18 patients, seven received placebo, three received doses of 5 mg once daily and eight received doses of 15 mg twice daily.
Dr. Lieberman said that the imaging study data will be presented April 12, 2010 to a meeting of the Schizophrenia International Research Society in Florence, Italy, by Dr. Daniel Javitt, Director of Cognitive Neuroscience and Schizophrenia at the Nathan Kline Institute for Psychiatric Research in Orangeburg, N.Y.
Dr. Javitt was lead investigator of the Phase 2a trial that was managed by TURNS (Treatment Units for Research on Neurocognition and Schizophrenia) with substantial financial support from the National Institute of Mental Health (NIMH), part of the U.S. National Institutes of Health.
About cognitive impairment associated with schizophrenia (CIAS)
In North America, Datamonitor estimates more than two million people have schizophrenia. In Europe, the European Federation of Associations of Families of People with Mental Illness estimates that 6.6 million people suffer from schizophrenia. While there are sales of $6-billion to treat the psychosis associated with schizophrenia, there are no approved drugs treating CIAS.
Most people with schizophrenia also suffer from this cognitive impairment, independent of the psychotic symptoms of the illness. Cognitive impairments are common at the onset of schizophrenia and can frequently be identified before psychotic symptoms emerge. In contrast to psychotic symptoms which are typically episodic, impairments in cognition appear to be a chronic feature of the illness.
Cognitive impairments are important as a treatment target because they have a substantial impact on the outcome of schizophrenia. Apart from psychotic symptoms, cognitive deficits in schizophrenia patients impact how they function, including social outcome, vocational outcome, and success in rehabilitation programs.
About davunetide
Davunetide is derived from a naturally occurring neuroprotective brain protein known as activity dependent neuroprotective protein (ADNP). Allon's laboratory and animal studies have shown that davunetide restores the function of structures in the brain - known as microtubules - which are critical to communication between brain cells and the structure of individual cells.
In 2008, Allon reported Phase 2a clinical trial results showing that davunetide had a statistically significant positive impact on memory function in patients with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer's disease (AD). The data was presented July 28 and July 30, 2008 to the International Conference on Alzheimer's Disease and Related Disorders (ICAD 2008).
On December 7, 2009, Allon reported Phase 2a clinical trial results showing that davunetide had a positive impact on the ability of schizophrenia patients to carry out important activities in their daily lives. The data was presented at the annual meeting of the American College of Neuropsychopharmacology.
About Allon's neuroprotective platforms
Allon's neuroprotective technology platforms are based on two naturally occurring proteins produced by the brain in response to a range of insults. The platforms are activity-dependent neuroprotective protein (ADNP) and activity-dependent neurotrophic factor (ADNF).
Because the two platforms are based on different proteins, the drugs from each are different molecules with different therapeutic mechanisms and distinct commercial opportunities. Clinical-stage drugs based on davunetide are derived from ADNP, while preclinical stage drug AL-309 is derived from ADNF. Davunetide is focused on Alzheimer's disease, cognitive impairment in schizophrenia, and progressive supranuclear palsy. ADNF drug candidate AL-309 is being developed for the treatment of peripheral neuropathies and is administered orally or subcutaneously.
About Allon
Allon Therapeutics Inc. is a clinical-stage biotechnology company developing treatments for major neurodegenerative conditions. Allon's drug davunetide has demonstrated human efficacy in amnestic mild cognitive impairment, a precursor to Alzheimer's disease, and cognitive impairment associated with schizophrenia. Allon has Phase II human efficacy programs pursuing large underserved markets, such as Alzheimer's disease and cognitive impairment associated with schizophrenia, and in orphan markets, such as frontotemporal dementias. The Company is listed on the Toronto Stock Exchange under the trading symbol "NPC" (Neuro Protection Company™) and based in Vancouver. For additional information please visit the Company's website: www.allontherapeutics.com.
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